Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity

Geng, Jing; Sun, Xiulian; Wang, Ping; Zhang, Shihao; Wang, Xiaozhen; Wu, Hongtan; Hong, Lian; Xie, Changchuan; Li, Xun; Zhao, Hao; Liu, Qingxu; Jiang, Mingting; Chen, Qinghua; Zhang, Jinjia; Li, Yang; Song, Shuai; Wang, Hongrui; Zhou, Rongbin; Johnson, Randy L.; Chien, Kun-Yi; Lin, Sheng-Cai; Han, Jiahuai; Avruch, Joseph; Chen, Lanfen; Zhou, Dawang

doi:10.1038/ni.3268

Cited by 222 publications

(240 citation statements)

References 49 publications

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“…As shown in Fig. 3A, TRAF6 in mock-infected cells displayed a diffused staining pattern in the whole cell, in agreement with the previous reports (27,28). Few autophagic vacuoles (i.e., GFP-LC3 puncta) could be detected in mock-infected cells.…”

Section: Suppression Of Traf6 Expression By Hcvsupporting

confidence: 80%

Suppression of Host Innate Immune Response by Hepatitis C Virus via Induction of Autophagic Degradation of TRAF6

Chan

Lee

Narula

et al. 2016

J Virol

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Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an important adaptor molecule that mediates the TNFR family and interleukin-1 (IL-1)/Toll-like receptor (TLR) signaling cascades. These pathways are important for the host to control viral infections. In this report, we demonstrated that hepatitis C virus (HCV) depleted TRAF6 from its host cells through a posttranslational mechanism. This depletion was independent of proteasomes, as it was not affected by the proteasome inhibitor MG132, but it was suppressed by bafilomycin A1, which led to the association of TRAF6 with autophagosomes. As bafilomycin A1 is a vacuolar ATPase inhibitor that inhibits autophagic protein degradation, these results suggested that HCV depleted TRAF6 via autophagy. The degradation of TRAF6 was apparently mediated by the p62 sequestosome protein, which is a factor important for selective autophagy, as it could bind to TRAF6 and its silencing stabilized TRAF6. The depletion of TRAF6 suppressed activation of NF-B and induction of proinflammatory cytokines and enhanced HCV replication. In contrast, the overexpression of TRAF6 suppressed HCV replication. These results revealed a novel mechanism that was used by HCV to disrupt the host innate immune responses for viral replication and persistence. IMPORTANCEHCV can cause severe liver diseases and is one of the most important human pathogens. It establishes chronic infections in the great majority of patients that it infects, indicating that it has evolved sophisticated mechanisms to evade host immunity. TRAF6 is an important signaling molecule that mediates activation of NF-B and expression of proinflammatory cytokines and interferons. In this study, we found that HCV infection suppressed the host innate immune response through the induction of autophagic degradation of TRAF6. This finding provided important information for further understanding how HCV evades host immunity to establish persistence.

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Section: Suppression Of Traf6 Expression By Hcvsupporting

confidence: 80%

Suppression of Host Innate Immune Response by Hepatitis C Virus via Induction of Autophagic Degradation of TRAF6

Chan

Lee

Narula

et al. 2016

J Virol

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“…In addition to ROS production by the NADPH oxidase complex, it has been shown that mitochondria-generated ROS is important for phagocyte-mediated bacterial killing, although L. monocytogenes was not used in this study (79). Furthermore, efficient phagosome localization with the mitochondria, mediated by the Mst1 and Mst2 kinases, is required for optimal induction of ROS downstream of TLR signaling, and mice lacking both Mst1 and Mst2 show increased susceptibility to L. monocytogenes compared to wild-type mice (80). …”

Section: Neutrophil Function During L Monocytogenes Infectionmentioning

confidence: 99%

The Essential Role of Neutrophils during Infection with the Intracellular Bacterial Pathogen Listeria monocytogenes

Witter

Okunnu

Berg

2016

The Journal of Immunology

108

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Neutrophils have historically been characterized as first responder cells vital to host survival due to their ability to contain and eliminate bacterial and fungal pathogens. However, recent studies have shown that neutrophils participate in both protective and detrimental responses to a diverse array of inflammatory and infectious diseases. Although the contribution of neutrophils to extracellular infections has been investigated for decades, their specific role during intracellular bacterial infections has only recently been appreciated. During infection with the gram-positive intracellular pathogen Listeria monocytogenes, neutrophils are recruited from the bone marrow to sites of infection where they utilize novel bacterial sensing pathways leading to phagocytosis and production of bactericidal factors. This review summarizes the requirement of neutrophils during Listeria monocytogenes infection by examining both neutrophil trafficking and function during primary and secondary infection.

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“…However, the regulation of YAP and TAZ by stress signals, such as energy stress, endoplasmic reticulum stress, and hypoxia, has been characterized only in the last couple of years, although activation of MST1/2 by a high concentration of sodium arsenite or heat shock was observed a long time ago (Taylor et al 1996). MST1/2 are also activated by hydrogen peroxide and are involved in cellular oxidative stress responses (Lehtinen et al 2006;Geng et al 2015). On the other hand, YAP physically interacts with FOXO1 and activates FoxO1-mediated transcription of catalase and MnSOD genes and subsequently reduces oxidative stress and ischaemia/reperfusion (I/R)-induced injury in the heart (Shao et al 2014), implicating a physiological role of YAP in reactive oxygen species (ROS) scavenging.…”

Section: Stress Signalsmentioning

confidence: 99%

Mechanisms of Hippo pathway regulation

2016

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The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway.

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Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity

Cited by 222 publications

References 49 publications

Suppression of Host Innate Immune Response by Hepatitis C Virus via Induction of Autophagic Degradation of TRAF6

Suppression of Host Innate Immune Response by Hepatitis C Virus via Induction of Autophagic Degradation of TRAF6

The Essential Role of Neutrophils during Infection with the Intracellular Bacterial Pathogen Listeria monocytogenes

Mechanisms of Hippo pathway regulation

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